IQ, Educational Attainment, Memory and Plasma Lipids: Associations with Apolipoprotein E Genotype in 5995 Children

MRC Centre for Causal Analyses in Translational Epidemiology, School of Social and Community Medicine, University of Bristol, Bristol, UK.
Biological psychiatry (Impact Factor: 10.26). 07/2011; 70(2):152-8. DOI: 10.1016/j.biopsych.2010.10.033
Source: PubMed


Apolipoprotein E (APOE) genotype (ε2/ε3/ε4: rs429358 ε4 allele; rs7412 ε2 allele) is strongly associated with both lipid levels and Alzheimer's disease. Although there is also evidence of milder cognitive impairment in later life in carriers of the APOE ε4 allele, there have been few studies investigating the impact of APOE genotype on cognitive function in children.
We determined APOE genotype in 5995 children from the Avon Longitudinal Study of Parents and Children and investigated associations between APOE genotype and plasma lipids (at age 9), IQ (at age 8), memory (at ages 8 and 10), and performance in school attainment tests (at ages 7, 11, and 14).
Observed genotype group counts were consistent with Hardy-Weinberg equilibrium (χ(2)p value = .84). There were strong relationships between APOE genotype and low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, which follow the same patterns as in adults. There was no strong evidence to suggest that APOE genotype was associated with IQ (all p values ≥ .46), memory function (p ≥ .35), or school attainment test results (p ≥ .28).
Although APOE genotype does have strong associations with lipid levels in childhood, there does not seem to be meaningful effects on cognitive performance, suggesting that any detrimental effects of the ε4 allele on cognitive function are not important until later life.

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Available from: Philip A I Guthrie
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    • "However, increasing the sample size with adolescent/young-adult populations has tended to decrease the likelihood that APOE effects are observed (Ihle et al., 2012). Importantly, a very well powered investigation (N & 4,000 children ) documented no significant effects of APOE on IQ, shortterm memory, working memory, or school achievement (Taylor et al., 2011), indicating that the present findings may also reflect a true null result and not a Type II error. "
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    • "For instance, previous works identified changes in the plasma cholesterol with the onset of mood/anxiety disorders and the modulation of memory performance (Peter et al, 2002;Henderson et al, 2003;Granholm et al, 2008). Even though the biological significance of these connections is not widely accepted and remains to be clarified because of the presence of contradictory data (Papakostas et al, 2004;Taylor et al, 2011;Reitz et al, 2005), we cannot exclude that changes in plasma lipids, also observed in our work, could have a role in the functional effects exerted by simvastatin administration. Moreover, a very recent paper showed that the enhancement of the autophagic flux alleviates memory deficits in a transgenic mouse model of AD (Li et al, 2013). "
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    • "Antagonist pleiotropy refers here to an age-dependent shift from positive to negative effects of a gene allele involved in complex traits. However , the beneficial effect of APOE-ε4 on cognitive performances at younger ages is still a matter of debate, most probably because of confounding factors inherent to human studies [7] [8]. An alternative approach is to investigate the cognitive effects of human APOE alleles in genetically engineered animals. "
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